Table 3.
TMI and TMLI Trials in Patients with Acute Leukaemia.
| Study* | Patients (N) age range (years) | Disease | Radiation targets | TMI dose (fractionation) | Chemotherapy | Outcomes |
|---|---|---|---|---|---|---|
| Wong et al. (317), Phase I, NCT00540995 |
20 23–52 |
Relapsed or refractory AML | Bone, nodes, testes, spleen 12 Gy: liver, brain |
12 or 13.5 Gy (1.5 BID) |
Bu 4,800 μM*min VP16 30 mg/kg |
NRM: 8 of 20 patients CR: 5 of 20 patients at 20.8–49.4 months |
| Stein et al. (311), Phase I, NCT02446964 |
51 16–57 |
AML, relapsed or refractory ALL | Bone, nodes, testes, spleen 12 Gy: liver, brain |
12–20 Gy (1.5–2.0 BID) |
Cy 100 mg/kg VP16 60 mg/kg |
NRM: 3.9% at day 100, 8.1% at 1 year PFS: 40% at 1 year OS: 55.5% at 1 year, 41.5% at 2 years |
| Stein et al. (311, 318), Phase II, NCT02094794 |
57 16–59 |
AML or ALL, IF, relapsed or >CR2 | Bone, spleen, node 12 Gy: liver, brain |
20 Gy (2.0 BID) |
Cy 100 mg/kg VP16 60 mg/kg |
NRM: 4% at day 100, 6% at 1 year PFS: 48% at 1 year OS: 67% at 1 year |
| Patel et al. (319), Phase I, NCT00988013 |
14 20–65 |
Refractory or relapsed AML, ALL, MDS, MM, CML | Bone | 3–12 Gy (1.5 BID) |
Flu 40 mg/m2/day × 4 Bu 4,800 μM*min |
NRM: 29% RFS: 43% OS: 50% |
| Hui et al. (320), Phase I, NCT00686556 |
12 2–55 |
High-risk ALL, AML CR2, CR3, relapse, IF |
Bone | 15 or 18 Gy (3.0 BID) |
Flu 25 mg/m2/day × 3 Cy 60 mg/m2/day × 2 |
NRM: 42% at 1 year Relapse rate: 36% DFS: 22% at 1 year OS: 42% at 1 year |
| Rosenthal et al. (309), Jensen et al. (321), Pilot, NCT00544466 |
61 9–70 |
AML, ALL >50 years old or comorbidities | Bone, nodes, spleen ALL: testes, brain |
12 Gy (1.5 BID) |
Flu 25 mg/m2/days × 4 Mel 140 mg/m2 |
NRM: 30% at 2 years, 33% at 5 years EFS: 49% at 2 years, 41% at 5 years OS: 50% at 2 years, 42% at 5 years |
| Welliver et al. (322), Pilot, NCT02122081 |
15 18–75 |
High-risk AML, ALL, MDS >50 years old or comorbidities and unable to undergo TBI-based regimens | Bone, brain, testes | 12 Gy (2.0 BID) |
Cy | NRM: 4 of 16 patients Median OS: 313 days |
| Al Malki et al. (323), Arslan and Al Malki (324), Phase I, NCT02446964 |
29 21–58 |
AML, ALL, MDS CR1 high risk, CR2, CR3, refractory Haplo-identical |
Bone, spleen, nodes 12 Gy: liver, spleen 16 Gy: testes in ALL 12 Gy: brain in ALL |
12–20 Gy (1.5–2.0 BID) |
Flu 25 mg/m2/day × 5 Cy 14.5 mg/kg/day × 2 PTCy 50 mg/kg/day × 2 |
NRM: 9.3% at 1 year OS: 83% at 1 year Relapse rate: 24% at 1 year |
| Pierini et al. (325), Phase II, NCT03977103 |
50 38–65 |
AML CR1, CR2, PR Haplo-identical |
Bone, nodes |
TMLI: bone 13.5 Gy; nodes 11.7 Gy if >50 years old TBI: 13.5 Gy in nine fractions or an 8 Gy single fraction if ≤50 years old |
Thio 5–10 mg/kg Flu 150–200 mg/m2 Cy 30 mg/kg/day T-cell manipulated graft |
NRM: 10 patients Relapse: 2 patients Moderate/severe cGvHD: 1 patient Moderate/severe cGvHD/RFS: 75% |
| Stein et al. (307), Pilot, NCT03467386 |
18 19–56 |
AML CR1 and CR2 Matched donor |
Bone, spleen, node 12 Gy: liver, brain |
20 Gy (2.0 BID) |
PTCy 50 mg/kg/day × 2 | Mild cGvHD: 5 patients OS: 100% at 1 year RFS: 80.8% at 1 year NRM: 0% at both day 100 and 1 year Relapse: 3 patients (16.7%) |
NCT numbers are Clinicaltrials.gov identifiers. AML, acute myeloblastic leukaemia; ALL, acute lymphoblastic leukaemia; BID, twice per day; Bu, busulfan; cGvHD, chronic graft-versus-host disease; CML, chronic myeloid leukaemia; CR1, first complete remission; CR2, second complete remission; CR3, third complete remission; Cy, cyclophosphamide; DFS, disease free survival; EFS, event-free survival; Flu, fludarabine; Gy, Gray; IF, induction failure; MDS, myelodysplastic syndrome; Mel, melphalan; MM, multiple myeloma; NRM, non-relapse mortality; OS, overall survival; PFS, progression-free survival; PR, partial response; PTCy, post-transplant cyclophosphamide; RFS, relapse-free survival; TBI, total body irradiation; Thio, thiotepa; TMI, total marrow irradiation; TMLI, total marrow and lymphoid irradiation; VP-16, etoposide.